Mycophenolate Mofetil for IgA Nephropathy

March 16, 2009 updated by: The University of Hong Kong

A Prospective, Randomized, Open Label, Case-Controlled Study on the Efficacy of Mycophenolate Mofetil for IgA Nephropathy Patients With Heavy Proteinuria Despite Angiotensin Blockade

IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide. In Hong Kong, IgAN accounts for approximately 30% of all primary glomerular diseases, and a significant proportion of young patients (< 50 years of age) on dialysis therapy are sufferers of primary IgAN. To date, no specific therapeutic agent has been consistently shown to halt the progression of IgAN to end-stage renal failure, particularly in patients with persistent significant proteinuria and the presence of chronic tubulointerstitial inflammation on kidney biopsy. In recent years, angiotensin-converting enzyme inhibitors (ACEI) have been found capable of significantly reducing proteinuria in some IgAN patients, while others, particularly those with the ACE DD genotype, showed either absent or unsatisfactory response to angiotensin blockade. Mycophenolate mofetil (MMF) is a marketed immunosuppressive drug which acts by releasing mycophenolic acid (MPA) to inhibit the de novo pathway of purine synthesis, and hence is relatively selective for lymphocytes. Apart from being efficacious for the prophylaxis of renal allograft rejection and for the induction of remission in severe lupus nephritis, MMF has been anecdotally reported to avert progression to allograft failure in recurrent IgAN of the transplanted kidney. Data on the clinical efficacy of MMF in the treatment of primary IgAN, however, is lacking. In the current proposal, we aim to study the clinical efficacy of MMF in patients with biopsy-proven IgAN and clinically significant proteinuria despite angiotensin blockade. Patients will be followed up for at least 5 years to track any survival difference between groups.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

(i) STUDY DESIGN

This will be a prospective, randomized, open-label, case-controlled study. Patients of either gender with biopsy-proven IgAN and clinically significant proteinuria despite being on ACEI treatment will be potential candidates (see selection criteria). Eligible patients will be randomized into either of the following groups:

Group I (Intervention arm):

Patients will be given MMF at a daily dose of 1.5 g orally in 2 divided doses in addition to concurrent medications, including ACEI. Duration of therapy is expected to be six months.

Group II (Control arm):

Patient will continue to receive all concurrent medications, including ACEI or angiotensin receptor blocker, at the discretion of the attending renal physician.

(ii) PATIENT SELECTION CRITERIA Inclusion criteria

  • Males or females between the ages of 18 and 70 years
  • Renal biopsy showing a histological diagnosis IgAN, with predominant or codominant mesangial deposition of IgA on immunofluorescent studies
  • Daily urinary protein excretion > 1 g on at least 3 separate occasions
  • Serum creatinine < 400 umol/L
  • Patients who are willing to give written informed consent and to participate in and comply with the study protocol

Exclusion criteria

  • Presence of concomitant glomerular diseases
  • Patients with known hypersensitivity to MMF
  • Patients receiving treatment with other cytotoxic agents
  • Serum creatinine > 400 umol/L
  • Women who are lactating, pregnant or of childbearing potential not using, or who are unwilling to use, a reliable contraceptive method during and for 6 weeks following conclusion of MMF therapy. A pregnancy test to exclude pregnancy will be performed for women of childbearing potential prior to recruitment
  • Patients who are unable or unwilling to give written informed consent and to participate in and comply with the study protocol
  • Presence of systemic infection or malignancy requiring therapy at the time of entry to the study
  • Patients simultaneously participating in another study or who have participated in another study within the last 30 days of entry into this study

(iii) PATIENT MONITORING

Patient record

The record of every recruited patient will contain the following information:

  • Demographic data
  • Medical history including concomitant illness
  • All concomitant medications
  • Other significant information

Timing of Assessments

All study assessments will be calculated from the date of study entry. The study follow-up schedule will be as follows:

  • Baseline, then
  • Two-weekly for the first month, then
  • Monthly for the 2nd - 6th month, at the end of which MMF will be withdrawn, then
  • Three-monthly until at least 5 years of follow up

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Hong Kong, China
        • Department of Medicine and Geriatrics, United Christian Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females between the ages of 18 and 70 years
  • Renal biopsy showing a histological diagnosis IgAN, with predominant or codominant mesangial deposition of IgA on immunofluorescent studies
  • Daily urinary protein excretion > 1 g on at least 3 separate occasions
  • Serum creatinine < 400 umol/L
  • Patients who are willing to give written informed consent and to participate in and comply with the study protocol

Exclusion Criteria:

  • Presence of concomitant glomerular diseases
  • Patients with known hypersensitivity to MMF
  • Patients receiving treatment with other cytotoxic agents
  • Serum creatinine > 400 umol/L
  • Women who are lactating, pregnant or of childbearing potential not using, or who are unwilling to use, a reliable contraceptive method during and for 6 weeks following conclusion of MMF therapy. A pregnancy test to exclude pregnancy will be performed for women of childbearing potential prior to recruitment
  • Patients who are unable or unwilling to give written informed consent and to participate in and comply with the study protocol
  • Presence of systemic infection or malignancy requiring therapy at the time of entry to the study
  • Patients simultaneously participating in another study or who have participated in another study within the last 30 days of entry into this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
MMF
Drug: mycophenolate mofetil
Orally at 0.75 g bd to 1 g bd for 6 months
Active Comparator: 2
Control
Drug: angiotensin blockade
Continuation of angiotensin blockade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
24 hour urinary protein excretion
Time Frame: 18 months to 5 years
18 months to 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Renal survival Serum creatinine level and creatinine clearance Urine albumin-to-creatinine ratio
Time Frame: at least 5 years
at least 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Collaborators

Queen Mary Hospital, Hong Kong
United Christian Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2002

Primary Completion (Actual)

June 1, 2004

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

March 15, 2009

First Submitted That Met QC Criteria

March 16, 2009

First Posted (Estimate)

March 17, 2009

Study Record Updates

Last Update Posted (Estimate)

March 17, 2009

Last Update Submitted That Met QC Criteria

March 16, 2009

Last Verified

March 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Roche-ST-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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